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Chemoprotection of transfer of multidrug resistance gene into human hematopoietic progenitor cell 被引量:3

Chemoprotection of transfer of multidrug resistance gene into human hematopoietic progenitor cell
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摘要 Objective To observe the effect of the transfer of multidrug resistance gene (mdr1) into human hematopoietic progenitor cells (HPC) on the chemoprotection Methods Human CD34 + cells served as a target of mdr1 gene transfer Retroviral vector SF mdr containing human total length mdr1cDNA was introduced into packing cells GP envAM12 by liposome mediated transfection The mdr1 gene was transduced into human CD34 + cells by retroviral supernatants of packing cells The integration and expression of the mdr1 gene and its protein (P170) in transduced cells were determined by PCR, RT PCR, and flow cytometry The drug resistance of chemotherapy in transduced HPC was determined by culturing colonies Results The mdr1 gene was integrated and expressed in transduced CD34 + cells The efficiency of mdr1 gene transfer was 10%-14% Compared with untransduced controls, within a certain range of drug concentration, the number of drug resistant colony in transduced HPC for taxol, doxorubicin,VCR and VP16 were increased by 3 6±2 1 fold, 2 9±0 3 fold, 1 9±0 4 fold, and 3 5±0 5 fold, respectively Conclusion The transfer of the mdr1 gene into human HPC can increase the drug resistance of the transduced cells to corresponding chemotherapeutic drugs that may provide some degree of chemoprotection for HPC Objective To observe the effect of the transfer of multidrug resistance gene (mdr1) into human hematopoietic progenitor cells (HPC) on the chemoprotection Methods Human CD34 + cells served as a target of mdr1 gene transfer Retroviral vector SF mdr containing human total length mdr1cDNA was introduced into packing cells GP envAM12 by liposome mediated transfection The mdr1 gene was transduced into human CD34 + cells by retroviral supernatants of packing cells The integration and expression of the mdr1 gene and its protein (P170) in transduced cells were determined by PCR, RT PCR, and flow cytometry The drug resistance of chemotherapy in transduced HPC was determined by culturing colonies Results The mdr1 gene was integrated and expressed in transduced CD34 + cells The efficiency of mdr1 gene transfer was 10%-14% Compared with untransduced controls, within a certain range of drug concentration, the number of drug resistant colony in transduced HPC for taxol, doxorubicin,VCR and VP16 were increased by 3 6±2 1 fold, 2 9±0 3 fold, 1 9±0 4 fold, and 3 5±0 5 fold, respectively Conclusion The transfer of the mdr1 gene into human HPC can increase the drug resistance of the transduced cells to corresponding chemotherapeutic drugs that may provide some degree of chemoprotection for HPC
出处 《Chinese Medical Journal》 SCIE CAS CSCD 2000年第6期56-59,共4页 中华医学杂志(英文版)
基金 ThisstudywassupportedbygrantsfromtheMinistryofPublicHealth,China!(No95150)
关键词 multidrug resistance gene hematopoietic progenitor cells HUMAN CHEMOPROTECTION multidrug resistance gene · hematopoietic progenitor cells, human · chemoprotection
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参考文献7

  • 1Fruehauf S,Wermann K,Buss EC,et al.Protection of hematopoietic stem cells from chemotherapy-induced toxicity by multidrug-resistance 1 gene transfer. Cancer Research . 1998
  • 2Gottesman M.How cancer cells evade chemotherapy:Sixteenth Richard and Hinda Rosenthal Foundation award lecture. Cancer Research . 1993
  • 3Galipeau J,Benaim E,Spencer HT et al.A bicistronic retroviral vector for prtecting hematopoietic cells against antifolates and P-glycoprotein effluxed drugs. Human Gene Therapy . 1997
  • 4Bertolini F,de Monte L,Corsini C,et al.Retrovirusmediated transfer of the multidrug resistance gene into human haemopoietic progenitor cells. British Journal of Haematology . 1994
  • 5Gottesman M,Pastan I.Biochemistry of multidrug resistance mediated by the multidrug transporter. Annual Review of Biochemistry . 1993
  • 6Koc ON,Allay JA,Lee K,et al.Transfer of drug resistance genes into hematopoietic progenitors to improve chemotherapy tolerance. Seminars in Oncology . 1996
  • 7Sorrentino BP,Brandt SJ,Bodine D,et al.Selection of drugresistant bone marrow cells in vivo after retroviral transfer of human MDR1. Science . 1992

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